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A joint deep learning model enables simultaneous batch effect correction, denoising, and clustering in single-cell transcriptomics.

ABSTRACT: Recent developments of single-cell RNA-seq (scRNA-seq) technologies have led to enormous biological discoveries. As the scale of scRNA-seq studies increases, a major challenge in analysis is batch effects, which are inevitable in studies involving human tissues. Most existing methods remove batch effects in a low-dimensional embedding space. Although useful for clustering, batch effects are still present in the gene expression space, leaving downstream gene-level analysis susceptible to batch effects. Recent studies have shown that batch effect correction in the gene expression space is much harder than in the embedding space. Methods such as Seurat 3.0 rely on the mutual nearest neighbor (MNN) approach to remove batch effects in gene expression, but MNN can only analyze two batches at a time, and it becomes computationally infeasible when the number of batches is large. Here, we present CarDEC, a joint deep learning model that simultaneously clusters and denoises scRNA-seq data while correcting batch effects both in the embedding and the gene expression space. Comprehensive evaluations spanning different species and tissues showed that CarDEC outperforms Scanorama, DCA + Combat, scVI, and MNN. With CarDEC denoising, non-highly variable genes offer as much signal for clustering as the highly variable genes (HVGs), suggesting that CarDEC substantially boosted information content in scRNA-seq. We also showed that trajectory analysis using CarDEC's denoised and batch-corrected expression as input revealed marker genes and transcription factors that are otherwise obscured in the presence of batch effects. CarDEC is computationally fast, making it a desirable tool for large-scale scRNA-seq studies.

SUBMITTER: Lakkis J

PROVIDER: S-EPMC8494213 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeImage quality of positron emission tomography (PET) is limited by various physical degradation factors. Our study aims to perform PET image denoising by utilizing prior information from the same patient. The proposed method is based on unsupervised deep learning, where no training pairs are needed.MethodsIn this method, the prior high-quality image from the patient was employed as the network input and the noisy PET image itself was treated as the training label. Constrained by the network structure and the prior image input, the network was trained to learn the intrinsic structure information from the noisy image and output a restored PET image. To validate the performance of the proposed method, a computer simulation study based on the BrainWeb phantom was first performed. A 68Ga-PRGD2 PET/CT dataset containing 10 patients and a 18F-FDG PET/MR dataset containing 30 patients were later on used for clinical data evaluation. The Gaussian, non-local mean (NLM) using CT/MR image as priors, BM4D, and Deep Decoder methods were included as reference methods. The contrast-to-noise ratio (CNR) improvements were used to rank different methods based on Wilcoxon signed-rank test.ResultsFor the simulation study, contrast recovery coefficient (CRC) vs. standard deviation (STD) curves showed that the proposed method achieved the best performance regarding the bias-variance tradeoff. For the clinical PET/CT dataset, the proposed method achieved the highest CNR improvement ratio (53.35% ± 21.78%), compared with the Gaussian (12.64% ± 6.15%, P = 0.002), NLM guided by CT (24.35% ± 16.30%, P = 0.002), BM4D (38.31% ± 20.26%, P = 0.002), and Deep Decoder (41.67% ± 22.28%, P = 0.002) methods. For the clinical PET/MR dataset, the CNR improvement ratio of the proposed method achieved 46.80% ± 25.23%, higher than the Gaussian (18.16% ± 10.02%, P < 0.0001), NLM guided by MR (25.36% ± 19.48%, P < 0.0001), BM4D (37.02% ± 21.38%, P < 0.0001), and Deep Decoder (30.03% ± 20.64%, P < 0.0001) methods. Restored images for all the datasets demonstrate that the proposed method can effectively smooth out the noise while recovering image details.ConclusionThe proposed unsupervised deep learning framework provides excellent image restoration effects, outperforming the Gaussian, NLM methods, BM4D, and Deep Decoder methods.

Project description:MotivationSingle-cell RNA sequencing (scRNA-seq) is an increasingly popular technique for transcriptomic analysis of gene expression at the single-cell level. Cell-type clustering is the first crucial task in the analysis of scRNA-seq data that facilitates accurate identification of cell types and the study of the characteristics of their transcripts. Recently, several computational models based on a deep autoencoder and the ensemble clustering have been developed to analyze scRNA-seq data. However, current deep autoencoders are not sufficient to learn the latent representations of scRNA-seq data, and obtaining consensus partitions from these feature representations remains under-explored.ResultsTo address this challenge, we propose a single-cell deep clustering model via a dual denoising autoencoder with bipartite graph ensemble clustering called scBGEDA, to identify specific cell populations in single-cell transcriptome profiles. First, a single-cell dual denoising autoencoder network is proposed to project the data into a compressed low-dimensional space and that can learn feature representation via explicit modeling of synergistic optimization of the zero-inflated negative binomial reconstruction loss and denoising reconstruction loss. Then, a bipartite graph ensemble clustering algorithm is designed to exploit the relationships between cells and the learned latent embedded space by means of a graph-based consensus function. Multiple comparison experiments were conducted on 20 scRNA-seq datasets from different sequencing platforms using a variety of clustering metrics. The experimental results indicated that scBGEDA outperforms other state-of-the-art methods on these datasets, and also demonstrated its scalability to large-scale scRNA-seq datasets. Moreover, scBGEDA was able to identify cell-type specific marker genes and provide functional genomic analysis by quantifying the influence of genes on cell clusters, bringing new insights into identifying cell types and characterizing the scRNA-seq data from different perspectives.Availability and implementationThe source code of scBGEDA is available at https://github.com/wangyh082/scBGEDA. The software and the supporting data can be downloaded from https://figshare.com/articles/software/scBGEDA/19657911.Supplementary informationSupplementary data are available at Bioinformatics online.

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A joint deep learning model enables simultaneous batch effect correction, denoising, and clustering in single-cell transcriptomics.

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